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Alcohol found to boost cancer risk by damaging stem cell DNA

8 January 2018
Appeared in BioNews 932

Drinking alcohol damages blood stem cells by altering their DNA, raising the risk of developing cancer, scientists have found.

A breakdown product of alcohol - acetaldehyde - is responsible for the damage, according to researchers at the MRC Laboratory of Molecular Biology in Cambridge. Acetaldehyde can cause irreversible DNA damage in blood stem cells, known as hematopoietic stem cells. These are the stem cells responsible for the constant production of fresh blood.

'How exactly alcohol causes damage to us is controversial,' said Professor Ketan Patel, who led the study which was published in Nature. 'This paper provides very strong evidence that an alcohol metabolite causes DNA damage [including] to the all-important stem cells that go on to make tissues.'

The link between alcohol and certain types of cancer has been known for some time, but exactly how drinking can raise cancer risk has been less clear. Acetaldehyde, a molecule produced by the breakdown of alcohol, badly damages DNA in cells, which in turn can lead to mutations and cancer, earlier studies have found. The cell has two ways of coping with the assault. 

First, acetaldehyde can be cleared away by the enzyme ALDH2 (aldehyde dehydrogenase 2). However, if more alcohol is consumed than the ALDH2 can deal with, then excess acetaldehyde can damage DNA. The second coping mechanism is to repair some of the DNA damage with an enzyme called FANCD2 (Fanconi anemia group D2 protein). 

In the study, the researchers used mice that did not possess either ALDH2 or FANCD2, or both, and gave them diluted alcohol for 10 days. They then sequenced the genome of their hematopoietic stem cells, to find that their DNA had been badly damaged. Hematopoietic stem cells from mice who had neither ALDH2 nor FANCD2 completely lost the ability to produce fresh blood.

'Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers,' said Patel. 'But it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact.'

Around 8 percent of the world's population, especially people of East Asian origin, have very low levels of ALDH2. This can lead to 'flushing' after drinking. As a result, there is more pressure on FANCD2, and may lead to more missed DNA damage. This could be an explanation for the high incidence of esophageal cancer in countries such as China. 

Professor Linda Bauld, an expert on cancer prevention at Cancer Research UK, said: 'This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover. We know that alcohol contributes to over 12,000 cancer cases in the UK each year, so it's a good idea to think about cutting down on the amount you drink.'

Cancer Research UK estimates that about 4 percent of cancers in the UK are caused by alcohol. One pint of lager or a large glass of wine a day significantly increases the risk of developing cancer.

Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells
Nature |  3 January 2018
Alcohol can cause irreversible genetic damage to stem cells, says study
The Guardian |  3 January 2018
Alcohol causes DNA damage in mice
NHS Choices |  4 January 2018
New research shows how alcohol damages DNA and increases cancer risk
CRUK |  3 January 2018
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